For a number of years inhalers have been used to deliver a metered dose of medicament to the respiratory tract of a patient. Basically there are three types of inhalers, adapted for powder medicament, aerosol driven fluid medicament and nebulisers.
The primary design of most of the inhalers are basically the same for the different forms of medicament; a housing containing a supply of the medicament, a mouthpiece, air flow conduits in connection with the supply of medicament and activating means for generating delivery of a metered dose of medicament. The activating means have a wide variety of constructions and functions. These include activation by the patients hand, such as squeezing the inhaler or maneuvering a button, during inhalation, electrically activated dose delivery, and inhalation activated dose delivery, for example.
Apart from delivery of a metered dose, most inhalers are also arranged with refilling/recharging means, that is, the chamber or compartment containing the metered dose has to be refilled/recharged after delivery, or before the next dose is to be delivered.
The drawback of the patient activated inhalers is that it may be difficult for some persons to activate the inhaler and inhale at the same instant. If these actions are not quite synchronised, the patient receives an inadequate amount of medicament into the respiratory tract. Many of the recent designs of inhalers are therefore breath activated wherein the device is activated by inhalation. This causes the canister to be depressed and deliver its metered dose.
One problem with these inhalers is that the canister remains depressed until the patient physically intervenes and removes the pressure on the canister. The chamber may not be refilled completely with these types of inhalers, especially when the amount remaining in the canister is low, because the user may hold the canister of the inhaler in a non-vertical position during the action activating/refilling of the inhalers metered dose chamber. If the level of medicament is low, it cannot then flow into the metered dose chamber in this position. Instead the chamber is filled with the propellant gas. During the subsequent dose, the patient will receive a reduced dose of medicament, perhaps only propellant gas.
Another problem with some breath-activated inhalers is that the inhaler allows for the canister to be compressed for substantial periods of time, resulting in reduced functionality of the valve mechanism.
Document U.S. Pat. No. 5,826,571 discloses a breath-activated inhaler comprising an activating means which depresses the canister in response to inhalation and return means for automatically deactivating or non-depressing the canister in response to the activating means. The inhaler further comprises control means for controlling the time the canister is open, i e the time between activation and deactivation. The return means also provides a refill of the metered dose chamber of the canister during deactivation.
One problem associated with the above inhaler is that the device controls the opening time of the canister, i e the time the canister is depressed, in order to insure that the whole dose is delivered. With the canisters presently on the market, the pressure is such that the major part of the metered dose is delivered during the first 200-300 ms after the canister opens. A remaining part is delivered during the subsequent period of time. For the previous breath-activated inhalers, the opening time posed no problem, since the canister remained open after activation until it was physically recharged. With the inhaler according to U.S. Pat. No. 5,826,571 the opening time controls the return means to deactivate the canister. A further aspect in this respect is the repeatability of the inhaler, which is one of the requirements of such a product from national authorities approving medicaments and products associated with these.
The opening time of U.S. Pat. No. 5,826,571 is controlled by a viscoelastic element. This element may be adjusted so that the required opening time is obtained when the inhaler is assembled at the factory, and even during some period of use. But repeated use, and time itself, will likely change the properties of the viscoelastic element so that the opening time varies. If shorter, the whole metered dose will not be delivered to the patient, with a deteriorated inhalation quality as a consequence due to doses delivered that are inadequate to the patient.
On the other hand, if the opening time is too long, the patient may remove the inhaler from the mouth and position it in a non-vertical position before the canister is closed and the metered dose chamber is closed. If the level of medicament then is low an inadequate refill of the chamber is obtained, as described above, and the patient does not receive its correct medicament during the subsequent inhalation.
A general problem with the known inhalers is that there is no possibility of monitoring or controlling the inhalation quality of the patient, and from that obtain an indication on the medication, since only the start of the inhalation activates the device.
Another aspect in this technical field is that many medical distribution products today have some sort of drug container comprising a number of doses of medicament and a drug delivery opening through which the medicament is delivered. For example these comprise inhalers such as aerosol inhalers where the medicament and propellant is contained in a canister or the like. The canister comprises a hollow stem through which the medicament is delivered when the stem is pressed into the canister. Other inhalers have the medicament in powder form, where the powder is contained in blisters or the like. When the medicament is to be delivered, the blister is opened, either by tearing the blister open or by piercing it so that an opening is created. With nebulisers, an ampoule or blister or other container holding the medicament is pierced or slit open.
Other medical distribution products are injectors where the medicament is contained in a syringe, which in turn is placed in a casing, which injectors automatically or semi-automatically perform different functions such as injecting the needle into the patient, delivering the medicament from the syringe and retracting the needle or ejecting a needle protector.
For the drug to be delivered from these devices, they are provided with some kind of actuating means. These often comprise springs or the like which could be “energised” i e tensioned and held in that state until they are released. The actuating means could be energised either manually by a lever, sliding button or the like tensioning the actuating means or automatically whereby they are tensioned by moving components of the device. In order to be held in an energised state, the devices comprise a locking means capable of holding the actuating means in an energised state. Depending on device, the actuating means, when released by the locking means, depress a canister, puncture a blister or ampoule or push the plunger of a syringe, etc.
The devices further comprise some sort of activating means operationally attached to the actuating means and capable of releasing the locking means when the patient is to receive a dose of medicament. These actuating means could be purely manually operated, such as a button, a lever or a handle arranged on the outer surface of the device. The patient then presses or moves the activating means in order to release the locking means.
For many inhalers, the activating means is a flap or a vane that is arranged adjacent an air intake on the inhaler and substantially blocking the air intake when not activated. When a patient inhales through an inhalation opening, a pressure difference occurs over the vane or flap. This pressure difference causes the flap or vane to move and thereby open the air intake so that an inhalation air flow is created. This movement of the flap or vane releases the locking means so that the actuating means is activated and a dose is delivered.
The spring means of the actuating means are often rather powerful. For instance with aerosol driven inhalers the spring means have to be able to depress the canister so that a dose is delivered. This means that a stem of the canister has to be pushed into the canister against the spring force of the stem and against the friction caused by the seals around the stem.
For auto-injectors there could be several actuating means. Firstly the needle has to be pushed into the patient. Then the plunger is pressed into the syringe in order to deliver the medicament. After the drug is delivered, the needle is withdrawn either by retracting it into the auto-injector housing or by pushing forward a needle protection means.
The fact that the force of the actuating means is relatively high and that it thus requires relatively high forces in order to hold or lock it in an energised state, at the same time as the forces for activating the actuating means need to be low, requires some form of transmission in order for the low activating force to be able to release the actuating force. It may be seen as one single energy system where a small input force provides a large output force.
Because of this relation, quite a number of components are required, which components will affect the energy system due to for example friction of components, tolerances and spring characteristics, giving rise to variations in force required for releasing the actuating means. Because it is one single interconnected system, the force for activating the activating means will thus also vary.
For most medical devices this is not acceptable because the activation should occur within a relatively narrow, well-defined force range. In order to cope with this, conventional techniques for these devices try to keep the number of components to a minimum and with high demands on tolerances in order to minimise the variations, in order to try to obtain predictable and repetitive conditions.
The strive to keep the number of component down and working with high tolerance requirements gives a rather costly device, by which it even so is difficult to manage all conditions.
One example is aerosol inhalers, where one, due to environmental considerations, is switching from canisters with CFC as propellant to HFA. HFA however requires much stronger seals whereby the force required to depress the canister may be substantially higher than for the CFC-canisters. With the same activating means, the variations will increase in the same degree. In order to cope with this, even higher demands on tolerances are required.
The above mentioned problems are also very much pronounced with some devices, such as multiple automatic functions acting in sequence of each other, with long and/or multiple energy systems where it is important that the forces required for triggering the different actuating means are certain to be provided without over-dimensioning the activating means. Otherwise, either it is not certain that the different functions are able to sequentially trigger each other or the device will be unnecessarily bulky and difficult to use.
According to a further aspect on inhalers, the main object with the breath-activation is to facilitate for the patient to obtain a dose of medicament, in comparison to the manually operated inhalers where the patient needs to activate the delivery by hand and inhale at the same time. This co-ordination of actions from the patient often causes problems so that, if the patient do not co-ordinate properly, the patient may not receive an adequate dose of medicament.
In the case of aerosol-driven inhalers the breath-activation causes a spring to compress a canister containing the medicament and propellant so that the medicament is delivered. Either a metered dose is delivered or the canister is open a predetermined time under which time medicament is delivered continuously. In the case of powder inhalers, the breath activation causes access to an amount of powder to be inhaled or a dose to be delivered. Other types of inhalers, such as nebulizers, may also have breath-activated devices for activating the delivery of a dose, or quantity, of medicament.
Some of the breath-activated devices comprise some form of plate-shaped lid, flap or vane movably arranged in an air flow path in the inhaler or adjacent an air intake. Upon inhalation the pressure drop and/or air flow causes the plate to move and thereby activate the actuating means so that a dose is delivered.
Some of the breath-activated inhalers are also arranged with return means. These return means “reset” the actuating means to a ready state so that the inhaler is ready for use for the subsequent inhalation. The return means also recharge the inhaler, e g refills a metered dose chamber with medicament for subsequent use. The return means are either operated manually, e g when a protective cover is closed or opened, or automatically, either at a specific time after inhalation or when the inhalation is terminated.
A drawback with the above described devices is that the breath-activated devices may unintentionally be triggered when the inhaler is ready for inhalation if the inhaler is dropped or otherwise exposed to sudden forces. Since the plates, vanes or flaps should be able to move by rather small forces exerted by the pressure drop/air flow during inhalation, they might also rather easily be moved by a sudden movement or sudden change of movement of the inhaler, such as if the inhaler is shaken or hits an object when it is ready for inhalation.
A number of doses important to the patient could be lost in this way. Further, the doses will, for many types of inhalers, be delivered inside the inhaler if triggered unintentionally. The medicament delivered inside the inhaler may deposit in passage ways or mechanisms of the inhaler and possibly obstruct the function or rendering the inhaler unclean. The deposition may also affect the dose-to-dose equivalence in that a lesser amount of medicament is inhaled than intended, and in that the deposited medicament may break loose during inhalation, whereby the amount is larger than intended.
In context with inhalers with automatic recharging means, an unintended triggering of the inhaler may also lead to an improper filling of the metered dose chamber if for example the inhaler is held in such a position during recharging that the medicament cannot properly fill the chamber. This could for example be the case with aerosol driven canisters that have to be held in a substantially vertical position when refilling the metered dose chamber, in particular when the canister is not full. The improper filling of the metered dose chamber leads to an improper dose delivered to the patient at the subsequent inhalation.
At the present, there is a wide variety of inhalers on the market, where a large quantity of these are so called aerosol-driven inhalers. These comprise a canister comprising the medicament and a gas as propellant. The canister comprises a dispensing device with a spring-loaded stem. When the stem is pressed into the canister, a metered dose of medicament is delivered.
Most aerosol-driven inhalers are provided with some activating means for depressing the canister. These span from simple levers pivotally arranged in the inhaler, which levers press on the side of the canister opposite the dispensing device, usually the bottom of the canister, to sophisticated arrangements comprising spring means acting on the canister, which springs are activated by inhalation. A recent type of inhaler also comprises motor means and control means together with a new type of canister, where the canister delivers medicament as long at it is depressed, and that the control means controls the motor which acts as depressing means for the canister. For example the control means controls the motor to keep the canister depressed for a certain period of time.
Usually, the canisters and the inhalers are manufactured by separate companies, where the canisters have different set dimensions and certain tolerance widths, and the stroke of the dispensing device has a certain stroke. On the market there are a few different canister sizes depending on the kind of medicament and the number of doses that each canister shall be able to deliver.
The manufacturers of inhalers have these canister measures to cope with when developing an inhaler, developing an inhaler for one specific canister size. Since the general aim for the developer of the inhaler is to keep the overall size as small as possible so that the inhaler is handy and discrete in use, the space inside the inhaler is rather limited. Especially when working with spring activating means it is not possible to use long springs in order to obtain a more or less constant spring characteristics during the depression movement of the canister. Instead transmission means are used to increase the spring force acting on the canister. These transmission means are however affected by differences in tolerances of the canister, of the inhaler, and of canister and inhaler together.
If, as an example, the canister has a tolerance width of a few millimeters over its entire length, which is not unusual, and the inhaler has an overall tolerance width of approximately one millimeter, this could lead to a total tolerance width of the system of several millimeters. With such tolerance widths, either the activating means will have to move quite a distance before coming in contact with a small canister, and thus exposing the canister to sudden impacts from the activating means, or, in the case of a large canister, that the activating means still contains a lot of energy when the canister is depressed. Since the starting point for the activating means varies so much with the tolerance widths built into the system and with the limited space available in the inhaler, it is very difficult to handle such differences and to design an activating means acting with the same predictable characteristics over this span.
Inhalers for inhaling medicament into the respiratory tract comprise some sort of opening, typically also with a mouthpiece, and an air flow passage inside the inhaler in communication with the opening. A compartment containing medicament and dose delivering means are also arranged and in communication with the air passage so that, when the patient inhales, air and medicament will mix in the air passage and will be inhaled by the patient.
A plurality of inhalers present on the market are provided with breath activated dose delivering means, so called breath activated inhalers. These function so as to deliver a dose of medicament when the patient inhales, i e when there is an air flow present in the air passage. In contrast to inhalers where the patient physically has to activate the dose delivering means, e g by pressing parts of the inhaler, manoeuvring levers and the like, the breath activated inhalers are triggered by the inhalation. This provides a more reliable dose delivery to the patient because the patient no longer has to time the inhalation with physical activation of the inhaler.
A drawback with these breath activated inhalers is unintentional or accidental activation of the inhaler, especially by children. A child often registers the activities of the adults and tries to do the same thing as them. If for example a parent uses an inhaler to inhale medicament, it is very likely that the child finds that interesting and would like to do the same. If the inhaler is then left within the child's reach it is likely that it would try to inhale. The inhaler would then be triggered to deliver a dose of medicament which the child unintentionally could inhale. Since these medicaments sometimes are quite potent, or even lethal, there is a risk that the child will suffer from poisoning which could lead to serious consequences.
According to yet another aspect of this technical area, inhalers for inhaling medicament comprise a body containing a supply of medicament, an air passage and a mouthpiece in contact with the air passage, wherein, upon use, the patient puts the mouthpiece in his mouth whereby a metered dose of medicament is dispensed in the air passage and inhaled by the patient.
The mouthpiece is generally a piece of pipe, either circular in cross-section or somewhat formed to correspond to the patients mouth, that is fixedly attached to, and protrudes from, the body of the inhaler.
In order to protect the mouthpiece when the inhaler is not in use, the inhaler is arranged with a protective cover or the like. In the simplest cases, the protective cover is a kind of capsule that can be pressed over the mouthpiece and is held in place by friction or snap-fit. A drawback with the capsule is that it is very easy to drop or loose it.
Most recent inhalers are provided with a protective-cover in the form of a lid pivotably arranged to the body of an inhaler. The lid is designed such that when in a protecting position, it encloses the mouthpiece protruding from the body, and when the inhaler is to be used, the lid is swung away so as to provide free access to the mouthpiece. With this design the protective means can not be dropped or lost since it is attached to the inhaler.
The general problem with the above inhalers is that the mouthpiece is fixedly attached to the inhaler body, making them rather bulky. A general desire from users is that the inhaler should be as small as possible so that it could be stored away conveniently when not in use, for example in the breast pocket or the like. This is not really the case with the present designs. Another desire from the users is that the inhaler should be easy to use in general and specifically easy and quick to activate as to inhale a dose. The activation of the inhaler may be critical if the patient suffers from a sudden reduction of the respiratory function. The inhaler must then be ready to use almost at an instant.